CRYSTALLINE FORM IV OF TILORONE DIHYDROCHLORIDE, AND INDUSTRIAL METHOD FOR ITS PRODUCTION (VERSIONS) Russian patent published in 2014 - IPC C07C217/24 C07C213/08 

FIELD: biotechnologies.

SUBSTANCE: stable crystalline substance corresponds to crystalline form IV of tilorone dihydrochloride, which is characterised by powder X-ray image, which has characteristic peaks at the following values of 2Θ(°): 6.48, 8.93, 10.13, 10.41, 12.99, 13.50, 13.92, 14.22, 16.41, 16.74, 18.20, 18.56, 18.89, 19.45, 19.94, 20.32, 22.33, 22.72, 23.59, 24.21, 25.64, 25.99, 26.35, 26.92, 27.45, 28.05, 29.85, 31.58. The invention also refers to versions of a method for obtaining crystalline form IV. The method involves cleaning of toluene solution of tilorone of the base from impurity of hydrophobic compound of 2-[2-(diethylamino)ethoxy]-7-[2-(ethylamino)ethoxy]-9H-fluorene-9-one, subsequent treatment with anhydride of dibasic carboxylic acid and alkali; with that, hydrophobic compound is converted to water-soluble salt that is removed by water washing. Then tilorone base is converted from toluene solution to solution of isopropyl alcohol and treated with concentrated hydrochloric acid with formation of crystals of tilorone dihydrochloride. Another method involves cleaning of toluene solution of tilorone base, which does not contain impurity of 2-[2-(diethylamino)ethoxy]-7-[2-(ethylamino)ethoxy]-9H-fluorene-9-one, by activated coal treatment. Then tilorone base is converted from toluene solution to solution of isopropyl alcohol and treated with concentrated hydrochloric acid and activated coal. Cleaned reaction mixture is cooled, and crystals of tilorone dihydrochloride are extracted.

EFFECT: composition can be used as an antivirus and immunomodulating substance; improved substance stability.

11 cl, 5 dwg, 3 tbl, 3 ex